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Hirsutism is characterized by the excessive growth of coarse hair in women, resembling the typical pattern seen in men. It affects between 5 to 10 % of females of reproductive age. Excessive hair growth often leads to significant mental and emotional anguish. Hirsutism is the result of an overabundance of androgens being secreted by the ovaries or adrenal glands. This article offers a comprehensive review of numerous causes that might provoke hirsutism which includes polycystic ovarian syndrome, Cushing syndrome, idiopathic hirsutism, insulin resistance, congenital adrenal hyperplasia, ovarian or adrenal tumors, menopause, and the use of certain drugs. Polycystic ovary syndrome and ovarian tumors are frequent underlying factors of hyperandrogenism, which subsequently results in the development of Hirsutism. Mechanical and cosmetic hair removal methods are viable options for managing hirsutism. This study examines the pharmacological therapies that have proven essential in enhancing the quality of life for patients. These treatments include oral contraceptives, antiandrogen therapy like spironolactone, cyproterone acetate, flutamide, and finasteride, specific insulin-lowering medicines, gonadotrophin-releasing hormone agonists, and topical treatment such eflornithine hydrochloride cream (13.9% w/w cream). This review also explored significance of nanotechnology-based methods like nanostructured lipid carriers, solid lipid nanoparticles, liposomes, cerosomes, and nanogel in enhancing the effectiveness of medications used to treat hirsutism. A comprehensive update has been made to the latest information on clinical studies and patents linked to the treatment of hirsutism.

Disease-modifying anti-rheumatic drugs (DMARDs) is a class of anti-rheumatic medicines that are frequently prescribed to patients suffering from rheumatoid arthritis (RA). Methotrexate, sulfasalazine, hydroxychloroquine, and azathioprine are examples of non-biologic DMARDs that are being used for alleviating pain and preventing disease progression. Biologic DMARDs (bDMARDs) like infliximab, rituximab, etanercept, adalimumab, tocilizumab, certolizumab pegol, and abatacept have greater effectiveness with fewer adverse effects in comparison to non-biologic DMARDs. This review article delineates the classification of DMARDs and their characteristic attributes. The poor aqueous solubility or permeability causes the limited oral bioavailability of synthetic DMARDs, while the high molecular weights along with the bulky structures of bDMARDs have posed few obstacles in their drug delivery and need to be addressed through the development of nanoformulations like cubosomes, nanospheres, nanoemulsions, solid lipid nanoparticles, nanomicelles, liposome, niosomes, and nanostructured lipid carrier. The main focus of this review article is to highlight the potential role of nanotechnology in the drug delivery of DMARDs for increasing solubility, dissolution, and bioavailability for the improved management of RA. This article also focusses on the different aspects of nanoparticles like their applications in biologics, biocompatibility, body clearance, scalability, drug loading, and stability issues.

Targeted therapy is highly desirable, as it allows for selective cytotoxicity on diseased cells without off-target side effects. Nucleolin is a remarkable target for cancer therapy given its high abundance, selective presence on the plasma membrane, and multifaceted influence on the initiation and progression of cancer. Nucleolin is a protein overexpressed on the cell membrane in many tumors and serves as a binding protein for several ligands implicated in angiogenesis and tumorigenesis. Nucleolin is present in the cytoplasm, nucleoplasm, and nucleolus and is used by selected pathogens for cell entry. AS1411 is a guanosine-rich oligonucleotide aptamer that binds nucleolin and is internalized in the tumor cells. AS1411 is well tolerated at therapeutic doses and localizes to tumor cells overexpressing nucleolin. AS1411 has a good safety profile with efficacy in relapsed acute myeloid leukemia and renal cell carcinoma producing mild or moderate side effects. The promising potential of AS1411 is its ability to be conjugated to drugs and nanoparticles. When a drug is bound to AS1411, the drug will localize to tumor cells leading to targeted therapy with fewer systemic side effects than traditional practices. AS1411 can also be bound to nanoparticles capable of detecting nucleolin at concentrations far lower than lab techniques used today for cancer diagnosis. AS1411 has a promising potential to change cancer diagnoses and treatment.

To create weed management techniques capable of improving agroecosystem sustainability, it is essential to comprehend the different weed flora composition and diversification dynamics in conservation agriculture production systems. In North Western Himalaya from 2018 to 2020, evaluation of various tillage techniques with and without residue incorporation and weed management techniques on diverse weed flora composition was performed. Fifteen treatment amalgamations of five tillages viz. CT (conventional tillage) in maize-CT in wheat, CT-ZT (ZT, zero tillage), ZT-ZT, ZT-ZTR (ZTR, zero tillage in amalgamation with remainder integration) & ZTR-ZTR and three weed management practices viz. H (suggested herbicide in maize)-H (suggested herbicide in wheat), IWM-IWM (IWM, integrated weed supervision) & HW-HW; (HW, hand weeding) were calculated in strip plot design. Significant differences (p = 0.05) of weed density and total weed count were recorded during summer (maize) and winter (wheat) seasons. Among tillage treatments, lowest weed population and total weed population were recorded in conservation tillage (ZTR-ZTR) in summer and conservative tillage followed by zero tillage in winter season (CT-ZT), respectively. IWM-IWM and H-H had a least weed population and total weed population in summer and winter seasons, respectively. Highest important value index during summer and winter seasons was recorded in Echinochloa colona (55.90%) and Avena ludoviciana (76.99%), respectively. Higher Shannon Wiener index and Evenness were recorded for CT+HW-CT+HW (1.83, 0.91) and ZT+IWM-ZTR+IWM (1.73, 0.86) which indicate higher weed species diversity during summer and winter seasons, respectively. ZTR-ZTR led to less diverse weed diversity compared to intensive conventional tillage (CT-CT) practices. However, higher Simpson’s diversity was recorded for CT+HW-CT+HW, i.e. 0.83 and 0.82 for maize and wheat, respectively, compared to the other conventional tillage treatments. This study helps in understanding the crop-weed relation such that the implementation of sound and economic weeds management strategies. Further, long-term experiments are required in order to interpret the complicated relationships of diverse weed species under different tillage and weed management strategies for sustainable and adoptive conservation agriculture production system for North Western Himalayas.

The study of protein-protein interactions (PPIs) and predicting the protein structure plays a critical role in understanding cellular processes and designing therapeutic interventions. In this research, we explore the application of quantum algorithms, specifically Grover’s algorithm, in improving the accuracy and efficiency of PPI prediction. By harnessing the inherent parallelism and quantum search capabilities of Grover’s algorithm, we aim to enhance the identification of interacting protein pairs from large-scale datasets. We demonstrate the effectiveness of using this algorithm through an extensive approach, comparing the performance of Grover’s algorithm with classical machine learning algorithms. Our results reveal that the quantum algorithm offers significant improvements in prediction accuracy, enabling the identification of previously undetected PPIs. Moreover, we discuss the advantages and limitations of using Grover’s algorithm in PPI prediction and provide insights into its potential for accelerating research in protein interaction networks. This research highlights the potential of quantum algorithms in advancing the field of bioinformatics and protein interaction analysis.

Abstract Natural disasters always have a damaging effect on our way of life. Landslides cause serious damage to both human and natural resources around the world. In this paper, the prediction accuracy of five hybrid models for landslide occurrence in the Uttarkashi, Uttarakhand (India) was evaluated and compared. In this approach, the Rough Set theory coupled with five different models namely Bayesian Network (HBNRS), Backpropagation Neural Network (HBPNNRS), Bagging (HBRS), XGBoost (HXGBRS), and Random Forest (HRFRS) were taken into account. The database for the models development was prepared using fifteen conditioning factors that had 373 landslide and 181 non-landslide locations that were then randomly divided into training and testing locations with a ratio of 75%:25%. The appropriateness and predictability of these conditioning factors were assessed using the multi-collinearity test and the least absolute shrinkage and selection operator approach. The accuracy, sensitivity, specificity, precision, and F-Measures, and the area under the curve (AUC)-receiver operating characteristics curve, were used to evaluate and compare the performance of the individual and hybrid created models. The findings indicate that the constructed hybrid model HXGBRS (AUC = 0.937, Precision = 0.946, F1-score = 0.926 and Accuracy = 89.92%) is the most accurate model for predicting landslides when compared to other models (HBPNNRS, HBNRS, HBRS, and HRFRS). Importantly, when the fusion is performed with the rough set method, the prediction capability of each model is improved. Simultaneously, the HXGBRS model proposed shows superior stability and can effectively avoid overfitting. After the core modules were developed, the user-friendly platform was designed as an integrated GIS environment using dynamic maps for effective landslide prediction in large prone areas. Users can predict the probability of landslide occurrence for selected region by changing the values of a conditioning factors. The created approach could be beneficial for predicting the impact of landslides on slopes and tracking landslides along national routes.

Replicative DNA polymerases are blocked by nearly all types of DNA damage. The resulting DNA replication stress threatens genome stability. DNA replication stress is also caused by depletion of nucleotide pools, DNA polymerase inhibitors, and DNA sequences or structures that are difficult to replicate. Replication stress triggers complex cellular responses that include cell cycle arrest, replication fork collapse to one-ended DNA double-strand breaks, induction of DNA repair, and programmed cell death after excessive damage. Replication stress caused by specific structures (e.g., G-rich sequences that form G-quadruplexes) is localized but occurs during the S phase of every cell division. This review focuses on cellular responses to widespread stress such as that caused by random DNA damage, DNA polymerase inhibition/nucleotide pool depletion, and R-loops. Another form of global replication stress is seen in cancer cells and is termed oncogenic stress, reflecting dysregulated replication origin firing and/or replication fork progression. Replication stress responses are often dysregulated in cancer cells, and this too contributes to ongoing genome instability that can drive cancer progression. Nucleases play critical roles in replication stress responses, including MUS81, EEPD1, Metnase, CtIP, MRE11, EXO1, DNA2-BLM, SLX1-SLX4, XPF-ERCC1-SLX4, Artemis, XPG, FEN1, and TATDN2. Several of these nucleases cleave branched DNA structures at stressed replication forks to promote repair and restart of these forks. We recently defined roles for EEPD1 in restarting stressed replication forks after oxidative DNA damage, and for TATDN2 in mitigating replication stress caused by R-loop accumulation in BRCA1-defective cells. We also discuss how insights into biological responses to genome-wide replication stress can inform novel cancer treatment strategies that exploit synthetic lethal relationships among replication stress response factors.

Integrated weed management strategies combine tillage systems and weed control strategies. Conservation agriculture (CA) and sustainable intensification cropping systems are potential sources of improved growth and overall productivity. This study evaluated tillage and weed management strategies effects on crop growth parameters and biological yields in maize-wheat cropping system in North Western Himalayan region. Different tillage (five) and weed management practices (three) were evaluated from 2018 to 2020 on growth indices and yield with fifteen treatments. Conservation agriculture (CA) based production system (ZT, zero tillage; crop rotation and intensification; residue management i.e. ZTR-ZTR) had higher crop dry matter accumulation (DMA), relative growth rate (RGR), crop growth rate (RGR) and biological yield of maize (28698 kg/ha) and wheat crops (18750 kg/ha). The zero tillage in maize and wheat (ZT-ZT) resulted in lowest maize (24677 kg/ha) and wheat biological yield (14009 kg/ha. Among weed management treatments, application of recommended herbicides in maize and wheat crop (H-H) resulted in higher crop DMA and biological yield of maize (27652 kg/ha) and wheat crop (19540 kg/ha). Therefore, for North Western Himalayan conditions, ZTR+H-ZTR+H (Conservation tillage combined with herbicide application in maize and wheat) is superior to other combinations for growth and yield.

Tuberculosis (TB) is still one of the most serious health issues today with a high fatality rate. While attempts are being made to make primary diagnosis more reliable and accessible in places with high tuberculosis rates, Chest X-rays has become a popular source. However, specialist radiologists are required for the screening process, which could be a challenge in developing countries. For early diagnosis of tuberculosis utilizing CXR images, a complete automatic system of tuberculosis detection can decrease the need for trained staff. Various deep learning and machine learning technologies have been introduced in recent years for examining digital chest radiographs for TB-related variances with the goal of reducing inter-class reader variability and reproducibility, as well as providing radiologic services in areas where radiologists are not available. Tuberculosis is sometimes misclassified as other conditions with similar radiographic patterns as a result of CXR images, resulting in inefficient therapy. The current approach, however, is limited to Computer-Aided Detection (CAD), which has only been evaluated with non-deep learning models. Deep neural networks open potentially new avenues for tuberculosis treatment. There are no peer-reviewed studies comparing the effectiveness of various deep learning systems in detecting TB anomalies, and none compare multiple deep learning systems with human readers. In this paper, the aim of the proposed method is to develop an efficient tuberculosis detection system based on stochastic learning with artificial neural network (ANN) model by random variations using Chest X-ray images. This approach can able to incorporate random functions into the network, either by assigning stochastic transfer functions to the network or by assigning stochastic weights to the network. This proposed method is to learn features from CXR images and optimize the parameters of an ANN model by randomly mixing the training dataset before each iteration, resulting in varied ordering of model parameter updates. Furthermore, in a neural network, model weights are frequently initialized at a random beginning point. By focusing on randomness functions with optimization, the proposed technique achieved great accuracy. The motivation of the proposed method is to detect abnormalities in CXR with the different levels of complexity of TB by strong or weak evidence with different deep geometric contexts such as shape, size, cavitation, and density. ANN’s primary benefit is extracting hidden linear and non-linear inter-relationships of high-dimensional and complex data. The proposed method was systematically tested with the Shenzhen and Montgomery datasets using metrics such as sensitivity, specificity, and accuracy, and it was discovered that the proposed method attained better accuracy when compared to state-of-the-art methods. The proposed method shows an improved efficiency with sensitivity of 96.12%, specificity of 98.01%, accuracy 98.45% and F-Score 95.88% respectively.

Objectives: To determine the socio-demographic and clinical profile of cancer patients developing radiation recall phenomenon or radiation recall dermatitis following chemotherapy administration, previously treated with external irradiation. We assessed its incidence, severity, frequency, differentiation from radio-sensitization and radiation-dermatitis, its correlation with radiation dose and chemotherapeutic agent, and various parameters affecting its occurrence. Materials and Methods: This observational prospective study was designed for 1092/2676 (50.2%) patients of histologically proven carcinoma breast, carcinoma lung, lymphomas, chest wall sarcomas, thymomas, thymic carcinomas, nasopharyngeal cancer, bladder carcinoma, rectal cancer, and metastatic cases who received radiation therapy followed by chemotherapy. Intake, treatment, observation, and follow-up were done from July 2014 to July 2021 for 7 years in two tertiary care cancer institutes of government setup. Results: In our study, majority of recall phenomena were reported in breast carcinoma 43/71 (60.5%) followed by carcinoma esophagus with 07/71 (9.8%) cases. Females developed 54.9% grade-I/II and 90% grade-III/IV recall cases compared to males with 45.1% and 10% cases, respectively (P = 0.005). Median radiation dose used was 45 Gy (dose range 8–70 Gy) (P = 0.656). Docetaxel resulted in 55% recall cases followed by paclitaxel with 12.7% of cases. Combination therapy reported 71.8% of cases compared to monotherapy with 28.2% of cases. Recall-cases recorded in the time period of 3–4 weeks between radiation and chemotherapy were 59/71 (83%) and those reported in >4 weeks were 12/71 (17%). Time-gap between 3 and 4 weeks reported 49% grade-I/II and 100% grade-III/IV recall-cases while time-gap >4 weeks resulted in 26% and 0% cases respectively (P = 0.000). Conclusion: In this study, taxanes and platinum-agents were the most common chemotherapeutic drugs involved in the occurrence of the recall phenomenon. Multi-drug regimens resulted in higher recall cases compared to monotherapy. Radiation dosage did not cause any significant impact. The risk and severity of recall reactions increased with female gender and shorter time-interval between radiation and systemic therapy, while early-onset recall cases displayed greater severity. This precedented but unpredictable phenomenon ceases to be a topic to be discarded in this modern era of highly conformal radiation therapy techniques and targeted cancer therapy.

Diabetes is a condition that affects a large percentage of the population and it is the leading cause of a wide range of costly complications. Diabetes is linked to a multi-fold increase in mortality and when compared to non-diabetics, the intensity and prevalence of COVID-19 ailment among diabetic individuals are more. Since its discovery in Wuhan, COVID-19 has grown rapidly and shown a wide range of severity. Temperature, lymphopenia, non-productive cough, dyspnoea, and tiredness are recognized as the characteristic of individuals infected with COVID-19 disease. In COVID-19 patients, diabetes and other related comorbidities are substantial predictors of disease and mortality. According to a recent study, SARS-CoV-2 (the virus responsible for covid-19 disease) may also lead to direct pancreatic harm, which could aggravate hyperglycemia and potentially cause the establishment of diabetes in formerly non-diabetic individuals. This bidirectional association of COVID-19 and diabetes load the burden on health care professionals throughout the world. It is recommended that gliptin medications be taken moderately, blood glucose levels must be kept under control, ACE inhibitors should be used in moderation, decrease the number of avoidable hospitalizations, nutritional considerations, and some other prevention measures, such as immunization, are highly recommended. SARS-CoV-2 may cause pleiotropic changes in glucose homeostasis, which could exacerbate the pathophysiology of pre-existing diabetes or result in new disease processes.

Homologous recombination DNA repair (HR) is a complex DNA damage repair pathway and an attractive target of inhibition in anti-cancer therapy. To help guide the development of efficient HR inhibitors, it is critical to identify compensatory HR sub-pathways. In this study, we describe a novel synthetic interaction between RAD51AP1 and RAD54L, two structurally unrelated proteins that function downstream of the RAD51 recombinase in HR. We show that concomitant deletion of RAD51AP1 and RAD54L further sensitizes human cancer cell lines to treatment with olaparib, a Poly (adenosine 5′-diphosphate-ribose) polymerase inhibitor, to the DNA inter-strand crosslinking agent mitomycin C, and to hydroxyurea, which induces DNA replication stress. We also show that the RAD54L paralog RAD54B compensates for RAD54L deficiency, although, surprisingly, less extensively than RAD51AP1. These results, for the first time, delineate RAD51AP1- and RAD54L-dependent sub-pathways and will guide the development of inhibitors that target HR stimulators of strand invasion.

The liver is a vital organ that plays a crucial role in the physiological operation of the human body. The liver controls the body’s detoxification processes as well as the storage and breakdown of red blood cells, plasma protein and hormone production, and red blood cell destruction; therefore, it is vulnerable to their harmful effects, making it more prone to illness. The most frequent complications of chronic liver conditions include cirrhosis, fatty liver, liver fibrosis, hepatitis, and illnesses brought on by alcohol and drugs. Hepatic fibrosis involves the activation of hepatic stellate cells to cause persistent liver damage through the accumulation of cytosolic matrix proteins. The purpose of this review is to educate a concise discussion of the epidemiology of chronic liver disease, the pathogenesis and pathophysiology of liver fibrosis, the symptoms of liver fibrosis progression and regression, the clinical evaluation of liver fibrosis and the research into nanotechnology-based synthetic and herbal treatments for the liver fibrosis is summarized in this article. The herbal remedies summarized in this review article include epigallocathechin-3-gallate, silymarin, oxymatrine, curcumin, tetrandrine, glycyrrhetinic acid, salvianolic acid, plumbagin, Scutellaria baicalnsis Georgi, astragalosides, hawthorn extract, and andrographolides.

Herbal drugs have been attracting much scientific interest in the last few decades and nowadays, phytoconstituents-based research is in progress to disclose their unidentified medicinal potential. Daidzein (DAI) is the natural phytoestrogen isoflavone derived primarily from leguminous plants, such as the soybean and mung bean, and its IUPAC name is 4′,7-dihydroxyisoflavone. This compound has received great attention as a fascinating pharmacophore with remarkable potential for the therapeutic management of several diseases. Certain pharmacokinetic properties of DAI such as less aqueous solubility, low permeability, and poor bioavailability are major obstacles restricting the therapeutic applications. In this review, distinctive physicochemical characteristics and pharmacokinetics of DAI has been elucidated. The pharmacological applications in treatment of several disorders like oxidative stress, cancer, obesity, cardiovascular, neuroprotective, diabetes, ovariectomy, anxiety, and inflammation with their mechanism of action are explained. Furthermore, this review article comprehensively focuses to provide up-to-date information about nanotechnology-based formulations which have been investigated for DAI in preceding years which includes polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, polymer-lipid nanoparticles, nanocomplexes, polymeric micelles, nanoemulsion, nanosuspension, liposomes, and self-microemulsifying drug delivery systems.

Despite presence of substantial evidence suggesting the pivotal role of amyloid (Aβ) in Alzheimer's disease (AD), very few therapeutic agents have been able to ameliorate the disease. This paved the way for the discovery of antibody-based immunotherapy to ace Aβ clearance and curb neuronal toxicity, resulting in revival of aducanumab, which following its entry into the brain, interacts with the parenchymal amyloid and decreases Aβ concentration, in a dose-dependent manner. However, the surprising approval from the FDA has created a controversy among healthcare professionals, due to Alzheimer's related imaging abnormality (ARIA) and hypersensitivity, serving as backlogs in its acceptance. Therefore, aducanumab is recognised as being “risen from the grave”, accompanied with contrasting statements within the healthcare paradigm. The manuscript provides a collection of data, aiming to elucidate, both the commendable and critical faces, simultaneously intending to gain the attention of the global researchers towards the possibility of disease-modifying therapy in AD. The manuscript discusses the failure of anti-amyloid therapies in AD, that have accelerated the need to find a suitable therapeutic approach, followed by the discussion of timeline and impact of aducanumab in AD models, alongside the controversial judgement raising significant question. Besides, the authors throw some light on the onco-therapeutic implications of the drug approval, which is identified as a significant consequence of the event. The text provides a holistic picture of the drug action, and enlists the considerations for the future, that might be beneficial to both the acceptance of the drug, and the treatment of the disease.

The 2019 corona virus disease (COVID-19) has caused a global chaos, where a novel Omicron variant has challenged the healthcare system, followed by which it has been referred to as a variant of concern (VOC) by the World Health Organization (WHO), owing to its alarming transmission and infectivity rate. The large number of mutations in the receptor binding domain (RBD) of the spike protein is responsible for strengthening of the spike-angiotensin-converting enzyme 2 (ACE2) interaction, thereby explaining the elevated threat. This is supplemented by enhanced resistance of the variant towards pre-existing antibodies approved for the COVID-19 therapy. The manuscript brings into light failure of existing therapies to provide the desired effect, however simultaneously discussing the novel possibilities on the verge of establishing suitable treatment portfolio. The authors entail the risks associated with omicron resistance against antibodies and vaccine ineffectiveness on one side, and novel approaches and targets – kinase inhibitors, viral protease inhibitors, phytoconstituents, entry pathways – on the other. The manuscript aims to provide a holistic picture about the Omicron variant, by providing comprehensive discussions related to multiple aspects of the mutated spike variant, which might aid the global researchers and healthcare experts in finding an optimised solution to this pandemic.

Protein misfolding causes aggregation and build-up in a variety of brain diseases. There are numeral molecules that are linked with the protein homeostasis mechanism. Molecular chaperones are one of such molecules that are responsible for protection against protein misfolded and aggregation-induced neurotoxicity. Many studies have explored the participation of molecular chaperones in Parkinson’s disease, Alzheimer’s disease, Amyotrophic lateral sclerosis, and Huntington’s diseases. In this review, we highlighted the constructive role of molecular chaperones in neurological diseases characterized by protein misfolding and aggregation and their capability to control aberrant protein interactions at an early stage thus successfully suppressing pathogenic cascades. A comprehensive understanding of the protein misfolding associated with brain diseases and the molecular basis of involvement of chaperone against aggregation-induced cellular stress might lead to the progress of new therapeutic intrusion-related to protein misfolding and aggregation.

Depression is one of the most debilitating psychiatric disorders affecting people of all ages worldwide. Despite significant heterogeneity between studies, increased inflammation and oxidative stress have been found in depression. Oxidative stress and inflammation are involved in the pathogenesis of depression. In the current review, we discussed the markers of oxidative stress and inflammation in depressive disorder and the association between these markers and the antidepressant treatment. The role of natural polyphenols in regulating various cell signaling pathways related to oxidative stress and inflammation has also been reviewed. The inhibitory effect of polyphenols on several cell signaling pathways reveals the vital role of polyphenols in the prevention and treatment of depressive disorder. Understanding the mechanism of polyphenols implicated in the regulation of cell signaling pathways is essential for the identification of lead compounds and the development of novel effective compounds for the prevention and treatment of depressive disorder.

Inflammatory myofibroblastic tumor (IMT) of lung is a rare tumor, accounting for ~0.7% of all lung tumors with varied clinical and radiological presentations. The origin of this tumor is unknown but some studies suggest that it might be a true neoplasm as some mutations on chromosome 2p23 of anaplastic lymphoma kinase (ALK) have been found to be related to this tumor. The morphology of IMT is quite vague and the histopathological diagnosis is predominantly given on excision specimens; in fact, only 6.3% of cases are diagnosed based on analysis of biopsy specimens alone. We illustrate a case of IMT diagnosed in a young male on core biopsy, where the case presented with a large tumor in the lung with metastases to multiple sites that was hence unresectable. Post 3 months of treatment with Crizotinib, there was significant reduction in the tumor size. Another interesting finding was that the ALK immunostain, which helped immensely in the diagnosis, was appreciated better on the Ventana platform rather than on the Dako platform.

Background: Fine-needle aspiration cytology plays role in preoperative diagnosis of any salivary gland mass lesions. Because of heterogeneity of salivary gland lesions and cytomorphology overlap, a uniform 6-tier Milan classification proposed which could be helpful in better communication of reports for patient's management. Methods: Study included 4 years (2011–2015) retrospective data retrieval from cytology department of our Institute, which is a tertiary care cancer center of South India. Histopathology correlation was done wherever possible. Result: Total 253 cases were studied. Histopathological follow-up was available in 115 cases. Cases were categorized as nondiagnostic (1.58%), nonneoplastic (13.43%), benign (30%), atypia (0.8%), and suspicious for malignancy and malignant cytology (51.8%). The risk for malignancy was high for suspicious for malignancy and malignant cytological categories ranged from 96–100%. The sensitivity, specificity, and accuracy for diagnosing malignancy varied from 86.76%, 93.75%, and 89%, respectively. Conclusion: Risk stratification approach in classifying salivary gland cytology aspirate as per Milan system provides a standardized reporting and better communication to clinician.

Cells respond to DNA damage by activating signaling and DNA repair systems, described as the DNA damage response (DDR). Clarifying DDR pathways and their dysregulation in cancer are important for understanding cancer etiology, how cancer cells exploit the DDR to survive endogenous and treatment-related stress, and to identify DDR targets as therapeutic targets. Cancer is often treated with genotoxic chemicals and/or ionizing radiation. These agents are cytotoxic because they induce DNA double-strand breaks (DSBs) directly, or indirectly by inducing replication stress which causes replication fork collapse to DSBs. EEPD1 and Metnase are structure-specific nucleases, and Metnase is also a protein methyl transferase that methylates histone H3 and itself. EEPD1 and Metnase promote repair of frank, two-ended DSBs, and both promote the timely and accurate restart of replication forks that have collapsed to single-ended DSBs. In addition to its roles in HR, Metnase also promotes DSB repair by classical non-homologous recombination, and chromosome decatenation mediated by TopoIIα. Although mutations in Metnase and EEPD1 are not common in cancer, both proteins are frequently overexpressed, which may help tumor cells manage oncogenic stress or confer resistance to therapeutics. Here we focus on Metnase and EEPD1 DNA repair pathways, and discuss opportunities for targeting these pathways to enhance cancer therapy.

Maize yield and weed concentration have a long history of reciprocal correspondence. The maize crop plant and weed species compete ruinously for nutrients, space, light, and water essential for their progress and advancement. The losses due to weed and methodologies of weed management have been discussed in this review. Reports have estimated around a 37% global loss in total maize production due to weeds. Among the different available weed control methods, chemical methods have become the new common in today’s world. A major upswing in interest in chemical methods of weed control from people all over the world can be deduced from surveys. The monetary forces that are the foremost objectives guiding our choices in crop production practices play a major role in this stimulation of increasing interest. These changes are not in the least befitting for the long term, as the overexploitation of the herbicides has an adverse effect on the environment and causes dismissal of the productivity of the soil, although being market-driven and favorable in the beginning. Since none of the single approach methods can work well enough on maize crops, integrated weed management and biological methodologies are recommended through several reports. In contrast to various weed management strategies, a significant gain in the academic attention of biological control methods can be reckoned from reports over the past few years. Many research projects are also currently underway.

This study addresses the problem of the automatic detection of disease states of the retina. In order to solve the abovementioned problem, this study develops an artificially intelligent model. The model is based on a customized 19-layer deep convolutional neural network called VGG-19 architecture. The model (VGG-19 architecture) is empowered by transfer learning. The model is designed so that it can learn from a large set of images taken with optical coherence tomography (OCT) and classify them into four conditions of the retina: (1) choroidal neovascularization, (2) drusen, (3) diabetic macular edema, and (4) normal form. The training datasets (taken from publicly available sources) consist of 84,568 instances of OCT retinal images. The datasets exhibit all four classes of retinal disease mentioned above. The proposed model achieved a 99.17% classification accuracy with 0.995 specificities and 0.99 sensitivity, making it better than the existing models. In addition, the proper statistical evaluation is done on the predictions using such performance measures as (1) area under the receiver operating characteristic curve, (2) Cohen’s kappa parameter, and (3) confusion matrix. Experimental results show that the proposed VGG-19 architecture coupled with transfer learning is an effective technique for automatically detecting the disease state of a retina.

The abundant synthesis and accretion of melanin inside skin can be caused by activation of melanogenic enzymes or increase in number of melanocytes. Melasma is defined as hyperpigmented bright or dark brown spots which are symmetrically distributed and have serrated and irregular borders. The three general categories of pigmentation pattern include centro facial pattern, malar pattern, and mandibular pattern. Exposure to UV rays, heat, use of cosmetics and photosensitizing drugs, female sex hormonal therapies, aberrant production of melanocyte stimulating hormone, and increasing aesthetic demands are factors which cause the development of melasma disease. This review gives a brief overview regarding the Fitzpatrick skin phototype classification system, life cycle of melanin, mechanism of action of anti-hyperpigmenting drugs, and existing pharmacotherapy strategies for the treatment of melasma. The objectives of this review are focused on role of cutting-edge nanotechnology-based strategies, such as lipid-based nanocarriers, i.e., lipid nanoparticles, microemulsions, nanoemulsions, liposomes, ethosomes, niosomes, transfersomes, aspasomes, invasomes penetration-enhancing vesicles; inorganic nanocarriers, i.e., gold nanoparticles and fullerenes; and polymer-based nanocarriers i.e., polymeric nanoparticles, polymerosomes, and polymeric micelles for the management of hyperpigmentation.

Cells must replicate and segregate their DNA to daughter cells accurately to maintain genome stability and prevent cancer. DNA replication is usually fast and accurate, with intrinsic (proofreading) and extrinsic (mismatch repair) error-correction systems. However, replication forks slow or stop when they encounter DNA lesions, natural pause sites, and difficult-to-replicate sequences, or when cells are treated with DNA polymerase inhibitors or hydroxyurea, which depletes nucleotide pools. These challenges are termed replication stress, to which cells respond by activating DNA damage response signaling pathways that delay cell cycle progression, stimulate repair and replication fork restart, or induce apoptosis. Stressed forks are managed by rescue from adjacent forks, repriming, translesion synthesis, template switching, and fork reversal which produces a single-ended double-strand break (seDSB). Stressed forks also collapse to seDSBs when they encounter single-strand nicks or are cleaved by structure-specific nucleases. Reversed and cleaved forks can be restarted by homologous recombination (HR), but seDSBs pose risks of mis-rejoining by non-homologous end-joining (NHEJ) to other DSBs, causing genome rearrangements. HR requires resection of broken ends to create 3’ single-stranded DNA for RAD51 recombinase loading, and resected ends are refractory to repair by NHEJ. This Mini Review highlights mechanisms that help maintain genome stability by promoting resection of seDSBs and accurate fork restart by HR.

The longstanding progressive neurodegenerative conditions of the central nervous system arise mainly due to deterioration, degradation and eventual neuronal cell loss. As an individual ages, the irreversible neurodegenerative disorders associated with aging also begin to develop, and these have become exceedingly prominent and pose a significant burden mentally, socially and economically on both the individual and their family. These disorders express several symptoms, such as tremors, dystonia, loss of cognitive functions, impairment of motor activity leading to immobility, loss of memory and many more which worsen with time. The treatment employed in management of these debilitating neurodegenerative disorders, such as Parkinson’s disease (which mainly involves the loss of dopaminergic neurons in the nigrostriatal region), Alzheimer’s disease (which arises due to accumulation of Tau proteins causing diffusive atrophy in the brain), Huntington’s disease (which involves damage of striatal and spinal neurons, etc.), have several adverse effects, leading to exploration of several lead targets and molecules existing in herbal drugs. The current review highlights the mechanistic role of natural products in the treatment of several neurodegenerative and cerebrovascular diseases such as Parkinson’s disease, Alzheimer’s disease, ischemic stroke and depression.

Cyclopentenone prostaglandins (cyPGs) are biologically active lipid mediators, including PGA2, PGA1, PGJ2, and its metabolites. cyPGs are essential regulators of inflammation, cell proliferation, apoptosis, angiogenesis, cell migration, and stem cell activity. cyPGs biologically act on multiple cellular targets, including transcription factors and signal transduction pathways. cyPGs regulate the inflammatory response by interfering with NF-κB, AP-1, MAPK, and JAK/STAT signaling pathways via both a group of nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) dependent and PPAR-γ independent mechanisms. cyPGs promote the resolution of chronic inflammation associated with cancers and pathogen (bacterial, viral, and parasitic) infection. cyPGs exhibit potent effects on viral infections by repressing viral protein synthesis, altering viral protein glycosylation, inhibiting virus transmission, and reducing virus-induced inflammation. We summarize their anti-proliferative, pro-apoptotic, cytoprotective, antioxidant, anti-angiogenic, anti-inflammatory, pro-resolution, and anti-metastatic potential. These properties render them unique therapeutic value, especially in resolving inflammation and could be used in adjunct with other existing therapies. We also discuss other α, β -unsaturated carbonyl lipids and cyPGs like isoprostanes (IsoPs) compounds.

The endoplasmic reticulum (ER) regulates protein folding, post-translational modifications, lipid synthesis, and calcium signaling to attenuate the accumulation of misfolded proteins causing ER stress and maintains cellular homeostasis. The tumor microenvironment is rich in soluble cytokines, chemokines, growth, and angiogenic factors and can drive the ER’s abnormal functioning in healthy cells. Cancer cells adapt well to the tumor microenvironment induced ER stress. We identified that the inflammatory breast cancer (IBC) cells abundantly express osteoprotegerin (OPG) and their tumor microenvironment is rich in OPG protein. OPG also called osteoclast differentiation factor/osteoclastogenesis inhibitory factor (OCIF) is a soluble decoy receptor for receptor activator of nuclear factor-kappa B ligand (RANKL). Employing mass spectrometry analysis, we identified a set of ER chaperones associated with OPG in IBC cell lysates (SUM149PT, SUM1315MO2) compared to healthy human mammary epithelial cells (HMEC). Proximity ligation assay (PLA) and immunoprecipitation assay validated the interaction between OPG and ER chaperone and master regulator of unfolded protein response (UPR) GRP78/BiP (glucose-regulated protein/Binding immunoglobulin protein). We detected remarkably high gene expression of CCAAT enhancer-binding protein homologous protein (CHOP), inositol-requiring enzyme 1 (IRE1α), protein disulfide-isomerase (PDI), PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4), X-box binding protein 1 (XBP-1) and growth arrest and DNA damage-inducible protein (GADD34) in SUM149PT and SUM190PT cells when compared to HMEC. Similarly, tissue sections of human IBC expressed high levels of ER stress proteins. We evaluated cell death and apoptosis upon Salubrinal and phenylbutyrate treatment in healthy and IBC cells by caspase-3 activity and cleaved poly (ADP-ribose) polymerase (PARP) protein assay. IBC (SUM149PT and SUM190PT) cells were chemosensitive to Salubrinal treatment, possibly via inhibition in OPG secretion, upregulating ATF4, and CHOP, thus ultimately driving caspase-3 mediated IBC cell death. Salubrinal treatment upregulated PDI, which connects ER stress to oxidative stress. We observed increased ROS production and reduced cell proliferation of Salubrinal treated IBC cells. Treatment with antioxidants could rescue IBC cells from ROS and aborted cell proliferation. Our findings implicate that manipulating ER stress with Salubrinal may provide a safer and tailored strategy to target the growth of inflammatory and aggressive forms of breast cancer.

Aim: This study was aimed at evaluation of antioxidative activity, protein profile, and vitamins content of milk of Gaddi goats, local non-Gaddi goats, hill cattle, and Jersey crossbred cattle. Materials and Methods: Total phenol, antioxidant activity measured as 2, 2-diphenyl- 1-picrylhydrazyl radical scavenging capacity, total protein, and vitamins were estimated in milk samples by spectrophotometric methods. Milk protein profiles were studied by sulfate-polyacrylamide gel electrophoresis. Results: Total phenol, antioxidant activity, and total protein were higher in indigenous hill cattle skim milk. Average protein content in raw skimmed milk was 1.33±0.01, 1.03±0.02, 0.76±0.05, and 0.81±0.01%, in indigenous hill cattle, Jersey crossbred cattle, non-Gaddi goat, and Gaddi goat, respectively. Three proteins of 19.01, 22.08, and 32.96 kDa were observed in Gaddi goat, but not in non-Gaddi goat skim milk. Furthermore, the above proteins were absent in cattle skim milk. Two proteins of 15.56 and 25.06 kDa were found in local hill and crossbred cattle skimmed milk, but were absent in goat skimmed milk. Vitamin C content was the lowest in Gaddi goat milk and the highest in Jersey crossbred cattle milk. Conclusion: It is envisaged that bioactive metabolites in the milk of Gaddi goats and hill cattle might offer anti-aging and beneficial health effects.

Fibrosis is a descriptive appellation referring to the obliteration of normal tissue components replaced by matrix and disorganized and varied collagen fibrils that result in the loss of organ function and frequent tissue contraction leading to death or significant deterioration in the quality of life. Radiation fibrosis syndrome (RFS) is a progressive fibrotic tissue sclerosis with various clinical symptoms in the irradiation field. It is usually a late complication of radiation therapy and may occur weeks or even years after treatment. It may affect the musculoskeletal, soft tissue, neural tissue, and cardiopulmonary systems. RFS is a serious and lifelong disorder that, nevertheless, may often be prevented when identified and rehabilitated early. Genetic factors likely play a significant role in the development of chronic fibrotic response to radiation injury that persists even after the initial insult is no longer present. Management of this syndrome is a complex process comprising medication, education, rehabilitation, and physical and occupational therapy. A bibliographical search was carried out in PubMed using the following keywords: “radiation fibrosis,” “radiation fibrosis syndrome,” and “radiation-induced fibrosis.” We also reviewed the most relevant and recent series on the current management of RFS, and the reviewed data are discussed in this article. This review discusses the pathophysiology, evaluation, and treatment of neuromuscular, musculoskeletal, and functional disorders as late effects of radiation treatment.

Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is underway. Berberine (BBR) is an isoquinoline alkaloid extracted from plants that possess a broad array of medicinal properties, including anti-diarrheal, anti-fibrotic, antidiabetic, anti-inflammatory, anti-obesity, antihyperlipidemic, antihypertensive, antiarrhythmic, antidepressant, and anxiolytic effects, and is frequently utilized as a traditional Chinese medicine. BBR promotes metabolisms of glucose and lipids by activating adenosine monophosphate-activated protein kinase, stimulating glycolysis and inhibiting functions of mitochondria; all of these ameliorate type 2 diabetes mellitus. BBR has also been shown to have benefits in congestive heart failure, hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, Alzheimer’s disease, and polycystic ovary syndrome. BBR has been investigated as an interesting pharmacophore with the potential to contribute significantly to the research and development of novel therapeutic medicines for a variety of disorders. Despite its enormous therapeutic promise, the clinical application of this alkaloid was severely limited because of its unpleasant pharmacokinetic characteristics. Poor bioavailability, limited absorption, and poor water solubility are some of the obstacles that restricted its use. Nanotechnology has been suggested as a possible solution to these problems. The present review aims at recent updates on important therapeutic activities of BBR and different types of nanocarriers used for the delivery of BBR in different diseases.

Herpesviruses utilize various host factors to establish latent infection, survival, and spread disease in the host. These factors include host cellular machinery, host proteins, gene expression, multiple transcription factors, cellular signal pathways, immune cell activation, transcription factors, cytokines, angiogenesis, invasion, and factors promoting metastasis. The knowledge and understanding of host genes, protein products, and biochemical pathways lead to discovering safe and effective antivirals to prevent viral reactivation and spread infection. Here, we focus on the contribution of pro-inflammatory, anti-inflammatory, and resolution lipid metabolites of the arachidonic acid (AA) pathway in the lifecycle of herpesvirus infections. We discuss how various herpesviruses utilize these lipid pathways to their advantage and how we target them to combat herpesvirus infection. We also summarize recent development in anti-herpesvirus therapeutics and new strategies proposed or under clinical trials. These anti-herpesvirus therapeutics include inhibitors blocking viral life cycle events, engineered anticancer agents, epigenome influencing factors, immunomodulators, and therapeutic compounds from natural extracts.

Wireless sensor networks (WSNs) are gaining popularity in applications like, defence, health monitoring and in agriculture etc. An efficiently design protocol can provide higher throughput, better stability period and longer network lifetime. In the similar context various protocols are proposed where much emphasis is given on minimization of energy used for per transmitted bit. Most of the designed protocols are based on two stages heterogeneous network consisting of two kinds of nodes; normal and advanced. The initial energy of the advanced nodes is higher in comparison to normal nodes. Generally, nodes form clusters and cluster head is utilized for the purpose of transferring packets to base station. Recently, stable election protocol (SEP) was proposed. In the case of SEP, both normal as well as advance nodes contain weighted probability to transform into cluster head. Advance nodes have more chances to be turned out as cluster head in comparison to normal nodes. To further enhance the performance of the protocol, Zonal-SEP is proposed, where field is divided into zones. In this paper, it is shown that, the concept of zones can be further extended into sectors and careful selection of sectors can further improves the performance with same number of advance nodes.

Extraskeletal myxoid chondrosarcoma (ESMC) is an extremely rare variant of chondrosarcoma accounting for less than 10% cases. It affects mainly the soft tissues of the proximal end of long bones. Its incidence in the head and neck region is less than 5%. This case presented in the nasopharynx, an exceedingly unusual site for ESMC in a 60-year-old female with left-sided nasal obstruction and occasional epistaxis of one-year duration. Biopsy from the nasopharyngeal mass was suggestive of low-grade chondrosarcoma. She underwent endoscopic resection of the tumor. Postoperative histopathology confirmed the diagnosis as myxoid chondrosarcoma of nasopharynx after performing a battery of immunohistochemical markers to rule out other possible differential diagnoses. We treated her with conformal adjuvant radiotherapy to a dose of 66 Gray in 33 fractions given residual disease to which she responded well with significant symptomatic and radiological improvement. The patient has been on regular follow-up for over two years without any evidence of recurrence or distant metastasis. This case is presented to highlight the extreme rarity, the clinicopathological findings of this disease, and to emphasize the role of radiotherapy as the primary adjuvant treatment affecting the final prognosis. A thorough review of the literature reveals that our case may be the second case of myxoid chondrosarcoma of nasopharynx ever reported in the world literature to date.

Objective: This cross-sectional, quantitative epidemiological study was aimed at finding out the degree of work-related stress among the staff nurses working in oncology. Methods: This study was conducted on 81 out of 100 oncology-trained nurses working in various oncology centers of Indian Army who consented to participate in it. It was carried out in five oncology centers of our organization where oncology-related facilities are available. Predesigned and pretested questionnaire covering their sociodemographic variables in part I and professional life stress scale by David Fontana in part II. The association between stress and various variables was found using Chi-square test. Results: Risk for professional stress was found more among unmarried young respondents of 20–30 years age group. No statistically significant association (P < 0.131) was found between department of posting and level of stress. Nurses reported that they had no time for rest, of whom 62.96% were suffering from moderate range of stress for a busy professional while only one admitted to have severe stress requiring remedial action. While 82.7% felt that they are able to achieve major objectives in life, 71.6% of them reported that they feel inadequately valued for their commitment at work. Conclusions: The main nurses' occupational stressors were criticism, feeling of not being appreciated for hard work, and having time for self. This type of assessment should be carried out in all hospitals so that working conditions for this important component of health care can be improved.

A Wireless Body Sensor Network (WBSN) characterizes an independent system that is used for the purpose of monitoring the daily routine activities of an individual. It comprises of smart sensor nodes which do not have any kind of adverse effect on the daily routine activities and are quite effective in the detection of chronic health problems such as diabetes, heart attack, asthma etc., and to caution the person suffering from diseases in the case of an emergency conditions. In this work, a wireless body area network routing protocol is designed where distance of the sink from various nodes and residual energy of the nodes decides the forwarding nodes to maximize the throughput. In this work, all the sensors on the body will transfer data to sink node and sink node will transmit data to base station or to the server. The simulation results will be evaluated in terms of remaining energy, throughput and number of dead nodes. The obtained results are also ompared with recent published protocols and it has been found that in comparison to SIMPLE and iM-SIMPLE, the proposed protocol E2 (nomenclature used in the paper) has throughput higher than 12.46% and 6.7% respectively.

Purpose: Dose received by organs at risk (OAR) in high-dose-rate (HDR) intracavitary brachytherapy (ICBT) for locally advanced cervical cancer impacts the late toxicity profile of the treatment. In the present study, we analyzed the inter-fraction variations of the minimum dose received by the most irradiated 2cc volumes (D2cc) of the OARs in ICBT. Methods and Materials: This prospective study included 40 patients with cervical cancer stage FIGO IIB-IVA treated with HDR ICBT and concomitant chemoradiotherapy with Computerized tomography (CT)- based three-dimensional planning. In addition, for 20 (of the 40) patients, the first fraction plan was superimposed on the second fraction images for studying its dosimteric impact on the OAR. The D2ccdata for the OAR was statistically analyzed for interfraction variations with Chi-square test or Fisher exact test as applicable. Paired t-test was used to compare the difference in means for the D2ccvalues between the three fractions. Results: The interfraction variations of the D2ccvalues of the OAR were statistically insignificant having P = 0.41, 0.8, and 0.20 for bladder, rectum, and sigmoid, respectively. Further, in 6 out of 20 cases, wherein first fraction plan was superimposed on second fraction images, the OAR doses exceeded the prescribed tolerance limits. Conclusion: We did not find variations in the OAR doses when each fraction was planned and treated individually. However, we found that if a single plan is used to treat subsequent fractions, OAR doses may exceed tolerance in about 30% of the cases. We believe that a larger sample size with improved compliance of bladder and bowel protocols would be needed to arrive at definitive conclusions.

The Curcuma longa plant is endowed with multiple traditional and therapeutic utilities and is here explored for its phytochemical constituents and cytotoxic potential. Turmeric rhizomes were extracted from three different solvents and screened for the presence of different phytochemical constituents, observation of which indicated that the polar solvents favoured extraction of greater versatile phytochemical constituents. These extracts were investigated for their cytotoxic potential by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on three different of cell lines including SCC-29B (oral cancer cell line), DU-145 (prostate cancer cell line) and the Vero cell line (healthy cell line/non-cancerous cell line). This assay was performed by taking three extracts from isolated curcuminoids and a pure bioactive compound bisdemethoxycurcumin (BD). Bisdemethoxycurcumin was isolated from curcuminoids and purified by column and thin-layer chromatography, and its structural characterisation was performed with different spectroscopic techniques such as FTIR, NMR (1H Proton and 13C Carbon-NMR) and LC-MS. Amongst the extracts, the ethanolic extracts exhibited stronger cytotoxic potential against the oral cancer cell line (SCC-29B) with an IC50value of 11.27 μg/mL, and that this was too low of a cytotoxicity against the Vero cell line. Although, curcuminoids have also shown a comparable cytotoxic potential against SCC-29B (IC50 value 16.79 μg/mL), it was not as potent against the ethanolic extract, and it was even found to be cytotoxic against healthy cell lines at a very low dose. While considering the isolated compound, bisdemethoxycurcumin, it also possessed a cytotoxic potential against the prostate cancer cell line (DU-145) (IC50 value of 93.28 μg/mL), but was quite safe for the healthy cell line in comparison to doxorubicin.

Psoriasis is a chronic inflammatory autoimmune disorder that moderately affects social and interpersonal relationships. Conventional treatments for psoriasis have certain problems, such as poor drug penetration through the skin, hyper-pigmentation, and a burning sensation on normal and diseased skin. Colloidal drug delivery systems overcome the pitfalls of conventional approaches for psoriasis therapeutics and have improved patient safety parameters, compliance, and superior effectiveness. They also entail reduced toxicity. This comprehensive review’s topics include the pathogenesis of psoriasis, causes and types of psoriasis, conventional treatment alternatives for psoriasis, the need for colloidal drug delivery systems, and recent studies in colloidal drug delivery systems for the treatment of psoriasis. This review briefly describes colloidal drug delivery approaches, such as emulsion systems—i.e., multiple emulsion, microemulsion, and nano-emulsion; vesicular systems—i.e., liposomes, ethosomes, noisomes, and transferosomes; and particulate systems—i.e., solid lipid nanoparticles, solid lipid microparticles, nano-structured lipid carriers, dendrimers, nanocrystals, polymeric nanoparticles, and gold nanoparticles. The review was compiled through an extensive search of the literature through the PubMed, Google Scholar, and ScienceDirect databases. A survey of literature revealed seven formulations based upon emulsion systems, six vesicular drug delivery systems, and fourteen particulate systems reported for antipsoriatic drugs. Based on the literature studies of colloidal approaches for psoriasis management carried out in recent years, it has been concluded that colloidal pharmaceutical formulations could be investigated broadly and have a broad scope for effective management of many skin disorders in the coming decades.

Adductomics novel and emerging discipline in the toxicological research emphasizes on adducts formed by reactive chemical agents with biological molecules in living organisms. Development in analytical methods propelled the application and utility of adductomics in interdisciplinary sciences. This review endeavors to add a new dimension where comprehensive insights into diverse applications of adductomics in addressing some of society’s pressing challenges are provided. Also focuses on diverse applications of adductomics include: forecasting risk of chronic diseases triggered by reactive agents and predicting carcinogenesis induced by tobacco smoking; assessing chemical agents’ toxicity and supplementing genotoxicity studies; designing personalized medication and precision treatment in cancer chemotherapy; appraising environmental quality or extent of pollution using biological systems; crafting tools and techniques for diagnosis of diseases and detecting food contaminants; furnishing exposure profile of the individual to electrophiles; and assisting regulatory agencies in risk assessment of reactive chemical agents. Characterizing adducts that are present in extremely low concentrations is an exigent task and more over absence of dedicated database to identify adducts is further exacerbating the problem of adduct diagnosis. In addition, there is scope of improvement in sample preparation methods and data processing software and algorithms for accurate assessment of adducts.

One of the utmost frequently emerging neurodegenerative diseases, Parkinson’s disease (PD) must be comprehended through the forfeit of dopamine (DA)-generating nerve cells in the substantia nigra pars compacta (SN-PC). The etiology and pathogenesis underlying the emergence of PD is still obscure. However, expanding corroboration encourages the involvement of genetic and environmental factors in the etiology of PD. The destruction of numerous cellular components, namely oxidative stress, ubiquitin-proteasome system (UPS) dysfunction, autophagy-lysosome system dysfunction, neuroinflammation and programmed cell death, and mitochondrial dysfunction partake in the pathogenesis of PD. Present-day pharmacotherapy can alleviate the manifestations, but no therapy has been demonstrated to cease disease progression. Peroxisome proliferator-activated receptors (PPARs) are ligand-directed transcription factors pertaining to the class of nuclear hormone receptors (NHR), and are implicated in the modulation of mitochondrial operation, inflammation, wound healing, redox equilibrium, and metabolism of blood sugar and lipids. Numerous PPAR agonists have been recognized to safeguard nerve cells from oxidative destruction, inflammation, and programmed cell death in PD and other neurodegenerative diseases. Additionally, various investigations suggest that regular administration of PPAR-activating non-steroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, indomethacin), and leukotriene receptor antagonists (montelukast) were related to the de-escalated evolution of neurodegenerative diseases. The present review elucidates the emerging evidence enlightening the neuroprotective outcomes of PPAR agonists in in vivo and in vitro models experiencing PD. Existing articles up to the present were procured through PubMed, MEDLINE, etc., utilizing specific keywords spotlighted in this review. Furthermore, the authors aim to provide insight into the neuroprotective actions of PPAR agonists by outlining the pharmacological mechanism. As a conclusion, PPAR agonists exhibit neuroprotection through modulating the expression of a group of genes implicated in cellular survival pathways, and may be a propitious target in the therapy of incapacitating neurodegenerative diseases like PD.

The blood–brain barrier is a major obstacle in treating brain-related disorders, as it does not allow the delivery of drugs into the brain. We developed a method for predicting blood–brain barrier penetrating peptides to facilitate drug delivery into the brain. These blood–brain barrier penetrating peptides (B3PPs) can act as therapeutics, as well as drug delivery agents. We trained, tested, and evaluated our models on blood–brain barrier peptides obtained from the B3Pdb database. First, we computed a wide range of peptide features. Then, we selected relevant peptide features. Finally, we developed numerous machine-learning-based models for predicting blood–brain barrier peptides using the selected features. The random-forest-based model performed the best with respect to the top 80 selected features and achieved a maximal 85.08% accuracy with an AUROC of 0.93. We also developed a webserver, B3pred, that implements our best models. It has three major modules that allow users to predict/design B3PPs and scan B3PPs in a protein sequence.

The human body is highly complex and comprises a variety of living cells and extracellular material, which forms tissues, organs, and organ systems. Human cells tend to turn over readily to maintain homeostasis in tissues. However, postmitotic nerve cells exceptionally have an ability to regenerate and be sustained for the entire life of an individual, to safeguard the physiological functioning of the central nervous system. For efficient functioning of the CNS, neuronal death is essential, but extreme loss of neurons diminishes the functioning of the nervous system and leads to the onset of neurodegenerative diseases. Neurodegenerative diseases range from acute to chronic severe life-altering conditions like Parkinson’s disease and Alzheimer’s disease. Millions of individuals worldwide are suffering from neurodegenerative disorders with little or negligible treatment available, thereby leading to a decline in their quality of life. Neuropathological studies have identified a series of factors that explain the etiology of neuronal degradation and its progression in neurodegenerative disease. The onset of neurological diseases depends on a combination of factors that causes a disruption of neurons, such as environmental, biological, physiological, and genetic factors. The current review highlights some of the major pathological factors responsible for neuronal degradation, such as oxidative stress, cell death, and neuroinflammation. All these factors have been described in detail to enhance the understanding of their mechanisms and target them for disease management.

Despite not being utilized as considerably as other antidepressants in the therapy of depression, the monoamine oxidase inhibitors (MAOIs) proceed to hold a place in neurodegeneration and to have a somewhat broad spectrum in respect of the treatment of neurological and psychiatric conditions. Preclinical and clinical studies on MAOIs have been developing in recent times, especially on account of rousing discoveries manifesting that these drugs possess neuroprotective activities. The altered brain levels of monoamine neurotransmitters due to monoamine oxidase (MAO) are directly associated with various neuropsychiatric conditions like Alzheimer’s disease (AD). Activated MAO induces the amyloid-beta (Aβ) deposition via abnormal cleavage of the amyloid precursor protein (APP). Additionally, activated MAO contributes to the generation of neurofibrillary tangles and cognitive impairment due to neuronal loss. No matter the attention of researchers on the participation of MAOIs in neuroprotection has been on monoamine oxidase-B (MAO-B) inhibitors, there is a developing frame of proof indicating that monoamine oxidase-A (MAO-A) inhibitors may also play a role in neuroprotection. The therapeutic potential of MAOIs alongside the complete understanding of the enzyme’s physiology may lead to the future advancement of these drugs.

Neuropathy is the least understood and most devastating complication associated with diabetes. Diabetic neuropathy develops in patients despite of regular therapy, indicating that marketed drugs has minimal effect on pathways leading to the development and progression of these complications. Present study was aimed to evaluate natural compounds for their ability to interfere with pathways leading to the development of diabetes mediated neurological complications and compare their efficacy with marketed anti-diabetic drugs. Anti-diabetic potential of ascorbic acid, gallic acid, quercetin, ellagic acid, cinnamic acid, caffeine and piperine was predicted by evaluating in-silico interaction energy (kcal/mol) of these compounds with insulin receptor, peroxisome proliferator-activated receptor gamma-γ and dipeptidyl peptidase-4 proteins. Ascorbic acid, gallic acid, quercetin and ellagic acid showed excellent in-vitro antioxidant activity in DPPH radical scavenging and inhibition of lipid peroxidation assay, which was 1.5–3 folds better than the marketed drugs. Quercetin, gallic acid, cinnamic acid, piperine and caffeine efficiently prevented H2O2 induced genotoxicity, which commercial drugs failed to prevent. Further, quercetin, ellagic acid, caffeine and ascorbic acid were 3–4.7 folds better than marketed drugs in inhibiting α-amylase activity. Herbal molecules and rosiglitazone showed comparable results for glucose uptake, which may be attributed to enhanced GLUT4 translocation into primary neuronal culture under hyperglycemic conditions. In conclusion, currently available marketed anti-diabetic drugs have minimal effect on the pathways leading to diabetic neuropathy and supplementing diabetic therapeutics with quercetin, ascorbic acid, caffeine and ellagic acid may be better suited to counter diabetic neuropathy through inhibiting oxidative stress, genotoxicity and improving neuronal glucose utilization.

Objective: The aim of this study was to assess the impact of radiotherapy (RT) on psychological, financial, and sexual aspects in postmastectomy carcinoma breast patients affecting their quality of life (QOL) before, during, and after RT with a strong emphasis on their management and rehabilitation aspects. Methods: A cross-sectional study carried out in a specialized institution, comprising sixty women. Two standardized questionnaires European Organization for Research and Treatment of Cancer (EORTC) 30-item Quality of Life Questionnaire and Quality of Life Questionnaire breast cancer-23 (QLQ-BR23) for health-related quality, translated and validated for the Hindi language were used. The scores' manual of the EORTC was used to calculate the domain scores of the questionnaires. Results: According to the first questionnaire, the emotional function was most affected even at onset of RT treatment and it was worst at the completion of RT treatment with a mean score of 63.75. The global QOL score was also worst at the end of radiation treatment with a mean score of 32.36, while the score 3 months after completion of treatment was 68.16. The symptoms with the highest scores were insomnia with a worst scoring at completion of treatment (29.99), fatigue (26.57), and pain (23.05). According to the QLQ-BR23, the mean score for side effects such as sexual functioning was minimum 0.55 at the completion of RT, which improved to 11.66 on the first follow-up after 3 months. Mean future perspective score which was 57.22 before the start of RT which was reduced to 50.55 at completion, which means that many women experience side effects of RT and impaired sexual satisfaction. Conclusions: Women with breast cancer showed changes in the following domains: financial, emotional, sexual satisfaction, and future prospects. The most frequently mentioned symptoms were fatigue, insomnia, and pain.

Solitary spinal metastasis with cord compression as the presenting feature of follicular thyroid carcinoma (FTC) is extremely unusual with

Objective: This descriptive and cross-sectional study was undertaken to determine the factors affecting quality of life (QOL) in breast cancer patients. Methods: We collected data from 60 patients of carcinoma breast post modified radical mastectomy on radiotherapy in a tertiary care hospital. We included volunteered patients with a signed informed consent and at least 70 Karnofsky Performance Scale points. The data was gathered by interview technique using EORTC QLQ-C30 and QLQ-BR23 (Breast Cancer Module). Results: The mean age at presentation was 47.6 years (range 30-75 years).75% patients were of low socio-economic status and 63.3% belonged to rural areas. Younger Women in the age group of 30-39 years had faired worst on physical, social and emotional scores as compared to older women in the age group of 70-79 years. Other factors which affected Quality of Life of patients during treatment were stage of disease at presentation, performance score of the patients, socioeconomic status of disease at follow up. Conclusion: Age, Education status, Performance Score, Stage of disease at presentation and status of disease at last follow up are few factors which significantly affects QOL in Carcinoma breast patients though the treatment remains same. Advanced studies on individual quality of life factors affecting cancer would empower physicians for better personal care techniques and patients for easily overcoming the disease.

Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, particularly latent infection is often associated with inflammation. The arachidonic acid pathway, the home of several inflammation and resolution associated lipid mediators, is widely altered upon viral infections. Several in vitro studies show that these lipid mediators help in the progression of viral pathogenesis. This review summarizes the findings related to human herpesvirus KSHV infection and arachidonic acid pathway metabolites. KSHV infection has been shown to promote inflammation by upregulating cyclooxygenase-2 (COX-2), 5 lipoxygenase (5LO), and their respective metabolites prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) to promote latency and an inflammatory microenvironment. Interestingly, the anti-inflammatory lipid mediator lipoxin is downregulated during KSHV infection to facilitate infected cell survival. These studies aid in understanding the role of arachidonic acid pathway metabolites in the progression of viral infection, the host inflammatory response, and pathogenesis. With limited therapeutic options to treat KSHV infection, use of inhibitors to these inflammatory metabolites and their synthetic pathways or supplementing anti-inflammatory lipid mediators could be an effective alternative therapeutic.

The hedgehog (SHH) signaling pathway is primarily involved in embryonic gut development, smooth muscle differentiation, cell proliferation, adult tissue homeostasis, tissue repair following injury, and tissue polarity during the development of vertebrate and invertebrate organisms. GLIoma-associated oncogene homolog (GLI) family of zinc-finger transcription factors and smoothened (SMO) are the signal transducers of the SHH pathway. Both SHH ligand-dependent and independent mechanisms activate GLI proteins. Various transcriptional mechanisms, posttranslational modifications (phosphorylation, ubiquitination, proteolytic processing, SUMOylation, and acetylation), and nuclear-cytoplasmic shuttling control the activity of SHH signaling pathway proteins. The dysregulated SHH pathway is associated with bone and soft tissue sarcomas, GLIomas, medulloblastomas, leukemias, and tumors of breast, lung, skin, prostate, brain, gastric, and pancreas. While extensively studied in development and sarcomas, GLI family proteins play an essential role in many host-pathogen interactions, including bacterial and viral infections and their associated cancers. Viruses hijack host GLI family transcription factors and their downstream signaling cascades to enhance the viral gene transcription required for replication and pathogenesis. In this review, we discuss a distinct role(s) of GLI proteins in the process of tumorigenesis and host-pathogen interactions in the context of viral infection-associated malignancies and cancers due to other causes. Here, we emphasize the potential of the Hedgehog (HH) pathway targeting as a potential anti-cancer therapeutic approach, which in the future could also be tested in infection-associated fatalities.